Partial volume correction in longitudinal tau PET studies: is it really needed?
Alejandro Costoya-Sánchez,
Alexis Moscoso,
Tomás Sobrino,
Álvaro Ruibal,
Michel J. Grothe,
Michael Schöll,
Jesús Silva-Rodríguez,
Pablo Aguiar
Affiliations
Alejandro Costoya-Sánchez
Molecular Imaging Group. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Av. Barcelona SN, 15782, Santiago de Compostela, Galicia, Spain; Nuclear Medicine Department and Molecular Imaging Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain
Alexis Moscoso
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Psychiatry and Neurochemistry, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden
Tomás Sobrino
NeuroAging Laboratory Group (NEURAL), Clinical Neurosciences Research Laboratories (LINC), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain
Álvaro Ruibal
Molecular Imaging Group. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Av. Barcelona SN, 15782, Santiago de Compostela, Galicia, Spain; Nuclear Medicine Department and Molecular Imaging Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain
Michel J. Grothe
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Psychiatry and Neurochemistry, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain; Reina Sofía Alzheimer's Centre, CIEN Foundation, ISCIII, Madrid, 28031, Spain
Michael Schöll
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Psychiatry and Neurochemistry, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden; Dementia Research Centre, Institute of Neurology, University College London, London, United Kingdom
Jesús Silva-Rodríguez
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain; Reina Sofía Alzheimer's Centre, CIEN Foundation, ISCIII, Madrid, 28031, Spain; Corresponding authors.
Pablo Aguiar
Molecular Imaging Group. Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela, Av. Barcelona SN, 15782, Santiago de Compostela, Galicia, Spain; Nuclear Medicine Department and Molecular Imaging Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Travesía da Choupana s/n, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain; Corresponding authors.
Background: [18F]flortaucipir (FTP) tau PET quantification is known to be affected by non-specific binding in off-target regions. Although partial volume correction (PVC) techniques partially account for this effect, their inclusion may also introduce noise and variability into the quantification process. While the impact of these effects has been studied in cross-sectional designs, the benefits and drawbacks of PVC on longitudinal FTP studies is still under scrutiny. The aim of this work was to study the performance of the most common PVC techniques for longitudinal FTP imaging. Methods: A cohort of 247 individuals from the Alzheimer's Disease Neuroimaging Initiative with concurrent baseline FTP-PET, amyloid-beta (Aβ) PET and structural MRI, as well as with follow-up FTP-PET and MRI were included in the study. FTP-PET scans were corrected for partial volume effects using Meltzer's, a simple and popular analytical PVC, and both the region-based voxel-wise (RBV) and the iterative Yang (iY) corrections. FTP SUVR values and their longitudinal rates of change were calculated for regions of interest (ROI) corresponding to Braak Areas I-VI, for a temporal meta-ROI and for regions typically displaying off-target FTP binding (caudate, putamen, pallidum, thalamus, choroid plexus, hemispheric white matter, cerebellar white matter, and cerebrospinal fluid). The longitudinal correlation between binding in off-target and target ROIs was analysed for the different PVCs. Additionally, group differences in longitudinal FTP SUVR rates of change between Aβ-negative (A-) and Aβ-positive (A+), and between cognitively unimpaired (CU) and cognitively impaired (CI) individuals, were studied. Finally, we compared the ability of different partial-volume-corrected baseline FTP SUVRs to predict longitudinal brain atrophy and cognitive decline. Results: Among off-target ROIs, hemispheric white matter showed the highest correlation with longitudinal FTP SUVR rates from cortical target ROIs (R2=0.28–0.82), with CSF coming in second (R2=0.28–0.42). Application of voxel-wise PVC techniques minimized this correlation, with RBV performing best (R2=0.00–0.07 for hemispheric white matter). PVC also increased group differences between CU and CI individuals in FTP SUVR rates of change across all target regions, with RBV again performing best (No PVC: Cohen's d = 0.26–0.66; RBV: Cohen's d = 0.43–0.74). These improvements were not observed for differentiating A- from A+ groups. Additionally, voxel-wise PVC techniques strengthened the correlation between baseline FTP SUVR and longitudinal grey matter atrophy and cognitive decline. Conclusion: Quantification of longitudinal FTP SUVR rates of change is affected by signal from off-target regions, especially the hemispheric white matter and the CSF. Voxel-wise PVC techniques significantly reduce this effect. PVC provided a significant but modest benefit for tasks involving the measurement of group-level longitudinal differences. These findings are particularly relevant for the estimations of sample sizes and analysis methodologies of longitudinal group studies.
